The present invention relates nuclear magnetic resonance (NMR) imaging; and more particularly, to a novel Rotational Exchange Gradient Imager (REGI) and methods for in situ magnetic resonance analyses, for example, in ultracentrifuge sedimentation of biological materials and rheology investigations of soft matter.
Nuclear magnetic resonance (NMR) analysis is a powerful method by which to determine chemical structures and to examine reaction dynamics in a diversity of chemical and biochemical systems.
For example, U.S. Pat. No. 5,574,370, issued Nov. 12, 1996 to Woelk et al., discloses a toroid cavity detection (TCD) system for determining the spectral properties and distance from a fixed point for a sample using Nuclear Magnetic Resonance. The detection system consists of a toroid with a central conductor oriented along the main axis of the toroidal cylinder and parallel to a static uniform magnetic field, B0. An RF signal is inputted to the central conductor to produce a magnetic field B1 perpendicular to the central axis of the toroid and whose field strength varies as the inverse of the radial position within the toroid. The toroid cavity detection system can be used to encapsulate a sample, or the detection system can be perforated to allow a sample to flow into the detection device or to place the samples in specified sample tubes. The central conductor can also be coated to determine the spectral properties of the coating and the coating thickness. The sample is then subjected to the respective magnetic fields and the responses measured to determine the desired properties.
U.S. Pat. No. 6,046,592, issued Apr. 4, 2000 to Rathke et al., discloses a near-electrode imager for employing nuclear magnetic resonance imaging to provide in situ measurements of electrochemical properties of a sample as a function of distance from a working electrode. The near-electrode imager uses the radio frequency field gradient within a cylindrical toroid cavity resonator to provide high-resolution nuclear magnetic resonance spectral information on electrolyte materials.
U.S. Pat. No. 6,191,583, issued Feb. 20, 2001 to Gerald II, discloses a toroid cavity detector that includes an outer cylindrical housing through which extends a wire along the central axis of the cylindrical housing from a closed bottom portion to the closed top end of the cylindrical housing. In order to analyze a sample placed in the housing, the housing is placed in an externally applied static main homogeneous magnetic field (B0). An RF current pulse is supplied through the wire such that an alternately energized and de-energized magnetic field (B1) is produced in the toroid cavity. The field B1 is oriented perpendicular to the field B0. Following the RF current pulse, the response of the sample to the applied field B0 is detected and analyzed. In order to minimize the detrimental effect of probe ringing, the cylindrically shaped housing is elongated sufficiently in length so that the top and bottom portions are located in weaker, fringe areas of the static main magnetic field B0. In addition, a material that tends to lessen the effect of probe ringing is positioned along the top and bottom ends of the toroid cavity. In another embodiment, a plug is positioned adjacent the inside of the top and bottom ends of the toroid cavity so that the sample contained in the toroid cavity is maintained in the strongest and most homogeneous region of the static magnetic field B0.
The subject matter of each of the U.S. Pat. Nos. 5,574,370, 6,046,592, and 6,191,583 is incorporated herein by reference.
A special type of NMR detector, a Magic Angle Spinning NMR (MAS NMR) detector can be used to examine solids. Analysis of solid materials by MAS NMR requires rapid rotation of the sample about the axis that defines an angle of 54.7xc2x0 with respect to the static magnetic field B0. Other researchers have used magic angle spinning NMR to study heterogeneous catalyzed reactions at elevated pressures. Several technical problems, however, limit the use of this technique. For flow-through reactions, which include most industrial processes, the need for rotating seals limits attainable pressures to xcx9c80 pounds per square inch (psi) (xcx9c5.5 kPa). Glass, plastic, or ceramic pressure vessels are brittle and further limit pressures to less than 100 psi (xcx9c6.9 kPa). Metal containers are thus necessary for the high pressures used in industrial applications, but they require that a radio frequency (RF) detector coil be positioned inside the container. Enclosing the RF coil in a metal container complicates the apparatus significantly because the electromagnetic field generated by the RF coil strongly interacts with the electronically conductive surfaces of the metal container. This electromagnetic interaction reduces the sensitivity and the overall performance of the detector.
At this time, several technical issues including the need for rotating seals and high pressures, and the like, limit the use of this high pressure MAS NMR technique. In situ investigations by NMR spectroscopy and imaging of the processes of sedimentation of proteins, deformations of soft materials, lubrication, and heterogeneous catalysis under high flow-through gas pressure have not been performed because a suitable device is not available.
A principal object of the present invention is to provide a novel Rotational Exchange Gradient Imager (REGI) for in situ nuclear magnetic resonance analyses, for example, in ultracentrifuge sedimentation of biological materials and rheology investigations of soft matter.
It is another object of the present invention to provide methods for in situ nuclear magnetic resonance analyses, for example, in ultracentrifuge sedimentation of biological materials and rheology investigations of soft matter.
It is another object of the present invention to provide a Rotational Exchange Gradient Imager (REGI) suitable for in situ investigations of the sedimentation process and constituent analyses of protein mixtures.
It is another object of the present invention to provide a Rotational Exchange Gradient Imager (REGI) suitable for investigations of soft matter under conditions where the material is deformed by the application of a large centrifugal force.
It is another object of the present invention to provide a Rotational Exchange Gradient Imager (REGI) suitable for spectroscopic analysis of a lubricant layer at the interfaces of a metal sleeve bearing under actual operating conditions.
It is another object of the present invention to provide a Rotational Exchange Gradient Imager (REGI) suitable for investigations of solid catalysts under conditions of high pressure and temperature, and flow of reactant gases through a catalyst bed.
It is another object of the present invention to provide a Rotational Exchange Gradient Imager (REGI) and method for implementing such Rotational Exchange Gradient Imager (REGI) substantially without negative effect and that overcome some disadvantages of prior art arrangements.
In brief, a novel detector and detecting methods are provided that expand the capabilities of Nuclear Magnetic Resonance (NMR) analysis and NMR analytical methods, allowing non-conventional materials to be examined using NMR in real time. A novel Rotational Exchange Gradient Imager (REGI) enables, for example, in situ magnetic resonance analyses in ultracentrifuge sedimentation of biological materials and rheology investigations of soft matter. The Rotational Exchange Gradient Imager (REGI) allows for real-time, in situ investigation of materials subjected to the effects of a centrifugal force by Nuclear Magnetic Resonance (NMR) analyses. The REGI comprises a cylindrical stator formed of an electrically conductive, non-magnetic material, a rotor contained in the cylindrical stator formed of an electrically non-conductive material, and a conductor located along a central axis of the cylindrical stator. A sample is contained within the rotor. The stator and central conductor serve to generate the RF magnetic field for NMR analysis. The rotor containing the sample is rotated within a stable air bearing formed between the cylindrical stator and rotor.
In a first embodiment of the invention, the rotor is driven by a high-pressure carrier gas jet containing reactant gas delivered to the inside of the stator via a closed loop formed of a pump and a pair of tubes, each tube coupled between the pump and a respective opening in the cylindrical stator. The central conductor and the cylindrical stator and rotor are held at a predefined magic angle relative to an externally applied static uniform magnetic field B0. Throughout the analysis, the sample contained within the rotor is rotated by the high-pressure carrier gas jet containing reactant gas, enabling accurate and precise control of the rotation frequency.
In a second embodiment of the invention, an air jet drives the rotor. In this embodiment, the central conductor is oriented along the main axis of the cylindrical stator and rotor and parallel to the static uniform magnetic field B0. An RF signal is inputted to the central conductor to produce a magnetic field B1 perpendicular to the central axis of the cylindrical stator and rotor. The produced magnetic field B1 is perpendicular to the static uniform magnetic field B0 and the predefined magic angle is not used.
In a third embodiment of the invention, a mechanical drive assembly drives the rotor. The mechanical drive assembly is coupled to the rotor and includes a drive motor and a drive gear. As in the second embodiment, a produced magnetic field B1 is perpendicular to the static uniform magnetic field B0 and the predefined magic angle is not used.
In accordance with features of the invention, the REGI allows real time NMR analysis and imaging of processes, enabling fast, easy, accurate, and precise adjustment of the rotation frequency and duration of the NMR analysis. REGI allows in situ NMR analysis and imaging of processes not possible before; for example, sedimentation of proteins, deformations of soft materials, lubrication, and heterogeneous catalysis under high flow-through gas pressure. The Rotational Exchange Gradient Imager (REGI) can provide highly detailed information, through NMR spectroscopy and imaging, in four diverse fields of science: molecular biology, rheology, tribology, and heterogeneous catalysis.